Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

References

• Adamson J, Azzopardi D, Errington G, et al. (2011). Assessment of an in vitro whole cigarette smoke exposure system: the Borgwaldt RM20S 8-syringe smoking machine. Chem Cent J 5:50–60.
   PubMed Web of Science ®Google Scholar
• Adamson J, Hughes S, Azzopardi D, et al. (2012). Real-time assessment of cigarette smoke particle deposition in vitro. Chem Cent J 6:98.
   PubMed Web of Science ®Google Scholar
• Adamson J, Thorne D, Errington G, et al. (2014). An inter-machine comparison of tobacco smoke particle deposition in vitro from six independent smoke exposure systems. Toxicol In Vitro 28:1320–8.
   PubMed Web of Science ®Google Scholar
• Adamson J, Thorne D, McAughey J, et al. (2013). Quantification of cigarette smoke particle deposition in vitro using a triplicate quartz crystal microbalance exposure chamber. Biomed Res Int 2013:685074.
   PubMed Web of Science ®Google Scholar
• Armitage AK, Dixon M, Frost BE, et al. (2004). The effect of inhalation volume and breath-hold duration on the retention of nicotine and solanesol in the human respiratory tract and on subsequent plasma nicotine concentrations during cigarette smoking. Beitr Tabakforsch Int 4:240–9.
   Google Scholar
• Azzopardi D, Haswell LE, Foss-Smith G, et al. (2015). Evaluation of an air-liquid interface cell culture model for studies on the inflammatory and cytotoxic responses to tobacco smoke aerosols. Toxicol In Vitro 29:1720–8.
   PubMed Web of Science ®Google Scholar
• Baker RR, Lewis LS. (2001). A review of the incidence and consequences of cigarette filter vent blocking among smokers. Beitr Tabakforsch Int 4:209–28.
   Google Scholar
• Behar RZ, Davis B, Wang Y, et al. (2014). Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids. Toxicol In Vitro 28:198–208.
   PubMed Web of Science ®Google Scholar
• Behar RZ, Hua M, Talbot P. (2015). Puffing topography and nicotine intake of electronic cigarette users. PLoS One 10:e0117222.
   PubMed Web of Science ®Google Scholar
• Bernstein DM. (2004). A review of the influence of particle size, puff volume, and inhalation pattern on the deposition of cigarette smoke particles in the respiratory tract. Inhal Toxicol 16:675–89.
   PubMed Web of Science ®Google Scholar
• Bombick DW, Bombick BR, Ayres PH, et al. (1997). Evaluation of the genotoxic and cytotoxic potential of mainstream whole smoke and smoke condensate from a cigarette containing a novel carbon filter. Fundam Appl Toxicol 39:11–7.
   PubMedGoogle Scholar
• Breheny D, Cunningham F, Kilford J, et al. (2014). Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants. Environ Mol Mutagen 55:662–72.
   PubMed Web of Science ®Google Scholar
• Borgwaldt, Smoking Machine RM20S. Available from: http://borgwaldt.hauni.com/en/instruments/smoking-machines/rotary/smoking-machine-rm20s.html [last accessed 1 June 2016].
   Google Scholar
• Brunnemann KD, Yu L, Hoffmann D. (1977). Assessment of carcinogenic volatile n-nitrosamines in tobacco and in mainstream and sidestream smoke from cigarettes. Cancer Res 37:3218–22.
   PubMed Web of Science ®Google Scholar
• Bullen C, McRobbie H, Thornley S, et al. (2010). Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tob Control 19:98–103.
   PubMed Web of Science ®Google Scholar
• Burns DM, Dybing E, Gray N, et al. (2008). Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal. Tob Control 17:132–41.
   PubMed Web of Science ®Google Scholar
• Caldwell B, Sumner W, Crane J. (2012). A systematic review of nicotine by inhalation: is there a role for the inhaled route? Nicotine Tob Res 14:1127–39.
   PubMed Web of Science ®Google Scholar
• Callahan-Lyon P. (2014). Electronic cigarettes: human health effects. Tob Control 23:ii36–40.
   PubMed Web of Science ®Google Scholar
• Chen IL. (2013). FDA summary of adverse events on electronic cigarettes. Nicotine Tob Res 15:615–6.
   PubMed Web of Science ®Google Scholar
• Cheng T. (2014). Chemical evaluation of electronic cigarettes. Tob Control 23:ii11–17.
   PubMed Web of Science ®Google Scholar
• Colard S, Verron T, Julien R, et al. (2014). Relationship between cigarette yields and smoking time under different machine smoking regimes. Beitr Tabakforsch Int 26:4–18.
   Google Scholar
• CORESTA. (2015). CORESTA recommended method No 81. Routine analytical machine for e-cigarette aerosol generation and collection – Definitions and Standard Conditions. CRM No 81. Available from: https://www.coresta.org/sites/default/files/technical_documents/main/CRM_81.pdf [last accessed 20 July 2016].
   Google Scholar
• Côté F, Létourneau C, Mullard G, Voisine R. (2011). Estimation of nicotine and tar yields from human-smoked cigarettes before and after the implementation of the cigarette ignition propensity regulations in Canada. Reg Tox Pharm 61:S51–S9.
   PubMed Web of Science ®Google Scholar
• Dautzenberg B, Bricard D. (2015). Real-time characterization of e-cigarettes use: the 1 million puffs study. J Addict Res Ther 6:2.
   Google Scholar
• Digard H, Proctor C, Kulasekaran A, et al. (2013). Determination of nicotine absorption from multiple tobacco products and nicotine gum. Nicotine Tob Res 15:255–61.
   PubMed Web of Science ®Google Scholar
• Eldridge A, Betson TR, Vinicius Gama M, McAdam K. (2015). Variation in tobacco and mainstream smoke toxicant yields from selected commercial cigarette products. Regul Toxicol Pharmacol 71:409–27.
   PubMed Web of Science ®Google Scholar
• European Commission. (2015). Special Eurobarometer 429: attitudes of Europeans towards tobacco and electronic cigarettes. Brussels: European Commission, 2015. Available from: http://ec.europa.eu/public_opinion/archives/ebs/ebs_429_en.pdf [last accessed 1 June 2016].
   Google Scholar
• European Commission. (2014). Directive 2014/40/EU of the European Parliament and of the Council. Available from: http://ec.europa.eu/health/tobacco/docs/dir_201440_en.pdf [last accessed 1 June 2016].
   Google Scholar
• Fagerström KO, Schildt EB. (2003). Should the European Union lift the ban on snus? Evidence from the Swedish experience. Addiction 98:1191–5.
   PubMed Web of Science ®Google Scholar
• Farsalinos KE, Romagna G, Tsiapras D, et al. (2013). Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities' regulation. Int J Environ Res Public Health 10:2500–14.
   PubMed Web of Science ®Google Scholar
• Farsalinos KE, Spyrou A, Tsimopoulou K, et al. (2014). Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices. Sci Rep 4:4133.
   PubMed Web of Science ®Google Scholar
• Farsalinos KE, Voudris V, Poulas K. (2015). E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction 110:1352–6.
   PubMed Web of Science ®Google Scholar
• Flick DA, Gonzalez-Rothi RJ, Ocie Harris J, Gifford GE. (1985). Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure. Cancer Res 45:5225–9.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). (2012). Guidance for industry and FDA staff: “harmful and potentially harmful constituents” in tobacco products as used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act. Federal Register, Vol. 77, No. 64. Available from: http://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM297981.pdf [last accessed 1 June 2016].
   Google Scholar
• Food and Drug Administration (FDA). (2013). Section 918 Report to Congress: innovative products and treatments to achieve abstinence from tobacco use, reductions in consumption of tobacco, and reductions in the harm associated with continued tobacco use. Available from: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/ucm348930.pdf [last accessed 12 July 2016].
   Google Scholar
• Food and Drug Administration (FDA). (2016). Deeming tobacco products to be subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the sale and distribution of tobacco products and required warning statements for tobacco products; Final Rule. Federal Register, Vol. 81, No. 90. Available from: https://www.gpo.gov/fdsys/pkg/FR-2016-05-10/pdf/2016-10685.pdf [last accessed 1 June 2016].
   Google Scholar
• Forster M, Liu C, Duke MG, et al. (2015). An experimental method to study emissions from heated tobacco between 100-200 °C. Chem Cent J 9:20.
   PubMed Web of Science ®Google Scholar
• Garcia-Canton C, Errington G, Anadon A, Meredith C. (2014). Characterisation of an aerosol exposure system to evaluate the genotoxicity of whole mainstream cigarette smoke using the in vitro γH2AX assay by high content screening. BMC Pharmacol Toxicol 15:41.
   PubMed Web of Science ®Google Scholar
• Gminski R, Tang T, Mersch-Sundermann V. (2010). Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards. Toxicol Lett 196:33–41.
   PubMed Web of Science ®Google Scholar
• Goniewicz ML, Knysak J, Gawron M, et al. (2014). Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 23:133–9.
   PubMed Web of Science ®Google Scholar
• Goniewicz ML, Lingas EO, Hajek P. (2013). Patterns of electronic cigarette use and user beliefs about their safety and benefits: an internet survey. Drug Alcohol Rev 32:133–40.
   PubMed Web of Science ®Google Scholar
• Hajek P, Goniewicz ML, Phillips A, et al. (2015). Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use. Nicotine Tob Res 17:175–9.
   PubMed Web of Science ®Google Scholar
• Health Canada. (1999). Official Method T-115 – Determination of “tar”, nicotine and carbon monoxide yields in mainstream smoke. Ottawa, QC: Health Canada. Available from: http://www.qp.gov.bc.ca/stat_reg/regs/health/oic_94.pdf [last accessed 1 June 2016].
   Google Scholar
• Health Canada. (2004). Official method T-503 – in vitro micronucleus assay for mainstream tobacco smoke. Ottawa, QC: Health Canada.
   Google Scholar
• Hiscock R, Goniewicz ML, McEwen A, et al. (2014). E-cigarettes: online survey of UK smoking cessation practitioners. Tob Induc Dis 12:13.
   PubMed Web of Science ®Google Scholar
• Hoffmann D, Wynder EL. (1967). The reduction of the tumorigenicity of cigarette smoke condensate by addition of sodium nitrate to tobacco. Cancer Res 27:172–4.
   PubMed Web of Science ®Google Scholar
• International Commission on Radiological Protection (ICPR). (1994). ICRP publication 66: human respiratory tract model for radiological protection; Elsevier health sciences. Ann ICRP 24:1–3.
   Google Scholar
• Ishikawa S, Suzuki T, Nagata Y. (2016). Analysis of cigarette smoke deposition within an in vitro exposure system for simulating exposure in the human respiratory tract. Beitr Tabakforsch Int 27:20–9.
   Google Scholar
• Iskandar AR, Martin F, Talikka M, et al. (2013). Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues. BioMed Res Int 2013:512086.
   PubMed Web of Science ®Google Scholar
• ISO. (1999). International Standard ISO 3402. Tobacco and tobacco products – Atmosphere for conditioning and testing. Geneva, Switzerland: International Organization for Standardization. Available from: http://www.iso.org/iso/catalogue_detail.htm?csnumber=28324 [last accessed 1 June 2016].
   Google Scholar
• ISO. (2000). International Standard ISO 4387. Cigarettes – Determination of total and nicotine-free dry particulate matter using routine analytical smoking machine. Geneva, Switzerland: International Organization for Standardization. Available from: http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=28323 [last accessed 1 June 2016].
   Google Scholar
• ISO. (2012). International Standard ISO 3308. Routine analytical cigarette-smoking machine – Definitions and standard conditions. Geneva, Switzerland: International Organization for Standardization. Available from: http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=60404 [last accessed 1 June 2016].
   Google Scholar
• Jackson KJ, Schroeder MJ, Hoffman AC. (2016). Mouth level exposure and similarity to machine-smoked constituent yields. Tob Regul Sci 2:3–8.
   PubMedGoogle Scholar
• Jin M, Earla R, Shah A, et al. (2012). A LC-MS/MS method for concurrent determination of nicotine metabolites and role of CYP2A6 in nicotine metabolism in U937 macrophages: implications in oxidative stress in HIV + smokers. J Neuroimmune Pharmacol 7:289–99.
   PubMed Web of Science ®Google Scholar
• Kaur N, Lacasse M, Roya J-P, et al. (2010). Evaluation of precision and accuracy of the Borgwaldt RM20S(®) smoking machine designed for in vitro exposure. Inhal Toxicol 22:1174–83.
   PubMed Web of Science ®Google Scholar
• Medicines and Healthcare products Regulatory Agency (MHRA). (2010). Nicotine replacement therapy and harm reduction. Drug Safety Update 3:6. Available at: https://www.gov.uk/drug-safety-update/nicotine-replacement-therapy-and-harm-reduction [last accessed 12 July 2016].
   Google Scholar
• Majeed S, Frentzel S, Wagner S, et al. (2014). Characterization of the Vitrocell® 24/48 in vitro aerosol exposure system using mainstream cigarette smoke. Chem Cent J 8:62.
   PubMed Web of Science ®Google Scholar
• Manigrasso M, Buonanno G, Stabile L, et al. (2015). Particle doses in the pulmonary lobes of electronic and conventional cigarette users. Environ Pollut 202:24–31.
   PubMed Web of Science ®Google Scholar
• Margham J, McAdam K, Forster M, et al. (2016). Chemical composition of an e-cigarette aerosol ? a quantitative comparison with cigarette smoke. Chem Res Toxicol. doi: 10.1021/acs.chemrestox.6b00188.
   PubMed Web of Science ®Google Scholar
• Mariner DC, Ashley M, Shepperd CJ, et al. (2011). Mouth level smoke exposure using analysis of filters from smoked cigarettes: a study of eight countries. Regul Toxicol Pharmacol 61:S39–S50.
   PubMed Web of Science ®Google Scholar
• Misra M, Leverette RD, Cooper BT, et al. (2014). Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols. Int J Environ Res Public Health 11:11325–47.
   PubMed Web of Science ®Google Scholar
• Neilson L, Mankus C, Thorne D, et al. (2015). Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol. Toxicol In Vitro 29:1952–62.
   PubMed Web of Science ®Google Scholar
• Nutt DJ, Phillips LD, Balfour D, et al. (2014). Estimating the harms of nicotine-containing products using the MCDA approach. Eur Addict Res 20:218–25.
   PubMed Web of Science ®Google Scholar
• Onoue S, Yamamoto N, Seto Y, Yamada S. (2011). Pharmacokinetic study of nicotine and its metabolite cotinine to clarify possible association between smoking and voiding dysfunction in rats using UPLC/ESI-MS. Drug Metab Pharmacokinet 26:416–22.
   PubMed Web of Science ®Google Scholar
• Palipudi KM, Mbulo L, GATS Collaborative Group, et al. (2016). Awareness and current use of electronic cigarettes in Indonesia, Malaysia, Qatar, and Greece: findings from 2011-2013 global adult tobacco surveys. Nicotine Tob Res 18:501–7.
   PubMed Web of Science ®Google Scholar
• Paur H-R, Cassee FR, Teeguarden J, et al. (2011). In vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—a dialog between aerosol science and biology. J Aerosol Sci 42:668–92.
   Web of Science ®Google Scholar
• Pepper J, Brewer N. (2014). Electronic nicotine delivery system (electronic cigarette) awareness, use, reactions and beliefs: a systematic review. Tob Control 23:375–84.
   PubMed Web of Science ®Google Scholar
• Phillips J, Kluss B, Richter A, Massey ED. (2005). Exposure of bronchial epithelial cells to whole cigarette smoke: assessment of cellular responses. Altern lab Anim 33:239–48.
   PubMed Web of Science ®Google Scholar
• Pichelstorfer L, Hofmann W, Winkler-Heil R, et al. (2016). Simulation of aerosol dynamics and deposition of combustible and electronic cigarette aerosols in the human respiratory tract. J Aerosol Sci 99:125–32.
   Web of Science ®Google Scholar
• Polosa R, Caruso M, Guarino F. (2016). Comments on Scheffler et al. cytotoxic evaluation of e-liquid aerosol using different lung derived cell models. Int J Environ Res Public Health 13:108.
   Web of Science ®Google Scholar
• Public Health England. (2015). E-cigarettes: an evidence update: a report commissioned by Public Health England. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf [last accessed 1 June 2016].
   Google Scholar
• Purkis SW, Troude V, Hill CA. (2013). Effect of puffing intensity on cigarette smoke yields. Regul Toxicol Pharmacol. 66:72–82.
   PubMed Web of Science ®Google Scholar
• Rickert WS, Trivedi AH, Momin RA, et al. (2007). Effect of smoking conditions and methods of collection on the mutagenicity and cytotoxicity of cigarette mainstream smoke. Toxicol Sci. 96:285–93.
   PubMed Web of Science ®Google Scholar
• Rodgman A, Perfetti TA. (2013). The chemical components of tobacco and tobacco smoke. 2nd ed. Boca Raton, (FL): CRC Press.
   Google Scholar
• Rodu B, Godshall WT. (2006). Tobacco harm reduction: an alternative cessation strategy for inveterate smokers. Harm Reduct J 3:37.
   PubMedGoogle Scholar
• Romagna G, Allifranchini E, Bocchietto E, et al. (2013). Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract. Inhal Toxicol 25:354–61.
   PubMed Web of Science ®Google Scholar
• Royal College of Physicians. (2016). Nicotine without smoke, Tobacco harm reduction, A report by the Tobacco Advisory Group of the Royal College of Physicians, April 28 2016, ISBN 978-1-86016-600-6 eISBN 978-1-86016-601-3. Available from: https://www.rcplondon.ac.uk/sites/default/files/media/Documents/Nicotine%20without%20smoke_0.pdf?token=uV0R0Twz [last accessed 1 June 2016].
   Google Scholar
• Sahu SK, Tiwari M, Bhangare RC, Pandit GG. (2013). Particle size distribution of mainstream and exhaled cigarette smoke and predictive deposition in human respiratory tract. Aerosol Air Qual Res 13:324–32.
   Web of Science ®Google Scholar
• Sangani RG, Ghio AJ. (2011). Lung injury after cigarette smoking is particle related. Int J Chron Obstruct Pulmon Dis 6:191–8.
   PubMed Web of Science ®Google Scholar
• Scheffler S, Dieken H, Krischenowski O, Aufderheide M. (2015). Cytotoxic evaluation of e-liquid aerosol using different lung-derived cell models. Int J Environ Res Public Health 12:12466–74.
   PubMed Web of Science ®Google Scholar
• Scheffler S, Dieken H, Krischenowski O, Aufderheide M. (2016). Response to Polosa et al. Comments on Scheffler et al. Cytotoxic Evaluation of E-Liquid Aerosol Using Different Lung Derived Cell Models. Int. J. Environ. Res. Public Health, 2015, 12, 12466-12474. Int J Environ Res Public Health 13:109. doi: 10.3390/ijerph13010109.
   Web of Science ®Google Scholar
• Schmid A, Baumlin N, Ivonnet P, et al. (2015). Roflumilast partially reverses smoke-induced mucociliary dysfunction. Respir Res 16:135.
   PubMed Web of Science ®Google Scholar
• Schoenborn CA, Gindi RM. “Electronic Cigarette Use Among Adults: United States, 2014,” National Center on Health Statistics (NCHS) Data Brief, No. 217, October 2015. Available from: http://www.cdc.gov/nchs/data/databriefs/db217.pdf [last accessed 1 June 2016].
   Google Scholar
• Schroeder MJ, Hoffman AC. (2014). Electronic cigarettes and nicotine clinical pharmacology. Tob Control 23:ii30–5.
   PubMed Web of Science ®Google Scholar
• Schweitzer K, Chen S, Law S, et al. (2015). Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures. Am J Physiology Lung Cell Mol Physiol 309:175–87.
   PubMed Web of Science ®Google Scholar
• Sosnowski TR, Kramek-Romanowska K. (2016). Predicted deposition of e-cigarette aerosol in the human lungs. J Aerosol Med Pulm Drug Deliv 29:299–309.
   PubMed Web of Science ®Google Scholar
• St Helen G, Havel C, Dempsey DA, et al. (2016). Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction 111:535–44.
   PubMed Web of Science ®Google Scholar
• Thorne D, Adamson J. (2013). A review of in vitro cigarette smoke exposure systems. Exp Toxicol Pathol 65:1183–93.
   PubMed Web of Science ®Google Scholar
• Thorne D, Dalrymple A, Dillon D, et al. (2015). A comparative assessment of cigarette smoke aerosols using an in vitro air–liquid interface cytotoxicity test. Inhal Toxicol 27:629–40.
   PubMed Web of Science ®Google Scholar
• Thorne D, Wilson J, Kumaravel TS, et al. (2009). Measurement of oxidative DNA damage induced by mainstream cigarette smoke in cultured NCI-H292 human pulmonary carcinoma cells. Mutat Res 673:3–8.
   PubMed Web of Science ®Google Scholar
• University of Kentucky: 3R4F reference cigarette. Available from: https://ctrp.uky.edu/resources/pdf/webdocs/3R4F%20Preliminary%20Analysis.pdf [last accessed 1 June 2016].
   Google Scholar
• Unwalla H, Ivonnet P, Dennis JS, et al. (2015). Transforming growth factor-b1 and cigarette smoke inhibit the ability of b2-agonists to enhance epithelial permeability. Am J Respir Cell Mol Biol 52:65–74.
   PubMed Web of Science ®Google Scholar
• US Department of Health and Human Services. (2010). Surgeon General’s report – how tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. Washington, (DC): Centers for Disease Control and Prevention.
   Google Scholar
• Varlet V, Farsalinos K, Augsburger M, et al. (2015). Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health 12:4796–815.
   PubMed Web of Science ®Google Scholar
• Vitrocell. VC10 Smoking Robot. Available from: http://www.vitrocell.com/inhalation-toxicology/smoking-machines/vc-10 [last accessed 1 June 2016].
   Google Scholar
• West R, Hajek P, Mcneill A, et al. (2015). Electronic cigarettes: what we know. A report to UK All Party Parliamentary Groups. Available from: http://www.smokinginengland.info/reports/ [last accessed 1 June 2016].
   Google Scholar
• World Health Organization. (2008). The scientific basis of tobacco product regulation: second report of a WHO study group. Geneva, Switzerland: World Health Organization Press, WHO Technical Report Series 951. Available from: http://apps.who.int/iris/bitstream/10665/43997/1/TRS951_eng.pdf?ua =1 [last accessed 1 June 2016].
   Google Scholar
• Williams M, Villarreal A, Bozhilov K, et al. (2013). Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol. PLoS One 8:e57987.
   PubMed Web of Science ®Google Scholar
• Yu V, Rahimy M, Korrapati A, et al. (2016). Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol 52:58–65.
   PubMed Web of Science ®Google Scholar